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Bioactive and biodegradable hydrogels that mimic the extracellular matrix and regulate valve interstitial cells (VIC) behavior are of great interest as three-dimensional (3-D) model systems for understanding mechanisms of valvular heart disease pathogenesis in vitro and the basis for regenerative templates for tissue engineering. However, the role of stiffness and adhesivity of hydrogels in VIC behavior remains poorly understood. This study reports the synthesis of methacrylated hyaluronic acid (Me-HA) and oxidized and methacrylated hyaluronic acid, and the subsequent development of hybrid hydrogels based on modified HA and methacrylated gelatin (Me-Gel) for VIC encapsulation. The mechanical stiffness and swelling ratio of the hydrogels were tunable with the molecular weight of the HA and the concentration/composition of the precursor solution. The encapsulated VIC in pure HA hydrogels with lower …